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In a previous report, the effectiveness of the Real Men Are Safe (REMAS) intervention in reducing the number of unprotected sexual occasions among male drug abuse treatment patients was demonstrated. A secondary aim of REMAS was to reduce the frequency with which men engage in sex under the influence (SUI) of drugs or alcohol.Men in methadone maintenance (n = 173) or out-patient psychosocial treatment (n = 104) completed assessments at baseline, 3 and 6 months post-intervention.The participants were assigned randomly to attend either REMAS (five sessions containing information, motivational exercises and skills training, including one session specifically targeting reducing SUI) or human immunodeficiency virus (HIV) education (HIV-Ed; one session containing HIV prevention information). SUI during the most recent sexual event served as the primary outcome in a repeated measures logistic regression model.Men assigned to the REMAS condition reporting SUI at the most recent sexual event decreased from 36.8% at baseline to 25.7% at 3 months compared to a increase from 36.9% to 38.3% in the HIV-Ed condition (tintervention = −2.16, P = 0.032). No difference between the treatment groups was evident at 6-month follow-up. At each assessment time-point, sex with a casual partner versus a regular partner, and being in methadone maintenance versus psychosocial out-patient treatment, were associated with engaging in SUI.Overall, a motivational and skills training HIV prevention intervention designed for men was associated with greater reduction in SUI than standard HIV education at the 3-month follow-up.